A Safety Study of YQ23 in Advanced Solid Tumors Patients
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|ClinicalTrials.gov Identifier: NCT04513067|
Recruitment Status : Recruiting
First Posted : August 14, 2020
Last Update Posted : September 14, 2020
This is an early phase dose escalation study which is divided into two stages: (1) Single agent of the test drug YQ23, and (2) in combination with pembrolizumab administered to patients with advanced solid tumors.
The purpose of the study is find out the safety and tolerability profile, as well as maximum tolerated dose (MTD) of YQ23 as single agent (stage 1) and in combination with pembrolizumab (stage 2). Stage 2 will start only when the MTD of single agent YQ23 has been established in Stage 1.
The distribution of YQ23 in the blood, the tumor response to YQ23 (and pembrolizumab in stage 2), the change of some pre-defined biomarkers in the tumor tissues and blood, and the change of antibody response and its relationship with the disease response, safety and drug level in the blood will also be evaluated.
In stage 1, eligible patients will be given intravenous infusion of YQ23 weekly for 4 weeks. In stage 2, eligible patients will be also be given a fixed dose of pembrolizumab 200 mg on Day 1 and every 3 weeks thereafter in addition to the weekly dose of YQ23. Dose escalation decision will be made based on the safety data available for the 4 weeks study treatment(s).
Patients may continue study treatment(s) beyond 4 weeks if s/he tolerates the study drug(s) well, the disease does not get worse after first 4 doses and meet all treatment continuation criteria, as judged by the study doctor.
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumor||Biological: YQ23 Combination Product: Pembrolizumab||Phase 1|
This is a phase 1b, open-label, dose-finding study to primarily evaluate the safety and tolerability, and MTD of YQ23 as a single agent and when in combination with pembrolizumab ("combo therapy") in patients with advanced malignant solid tumors of which it will have the potential to benefit from immunotherapy, such as triple negative breast cancer, colorectal cancer, liver cancer, non-small cell lung cancer, or renal cell carcinoma. In the study, the Pharmacokinetics (PK) profile and the disease response to YQ23 will be investigated while the Pharmacodynamics (PDx) profile and immunogenicity of YQ23 will be explored when YQ23 is given alone and in combo therapy.
The study composes of 2 stages. Stage 1 is a YQ23 alone dose escalation study; and Stage 2 is YQ23 in combination with pembrolizumab dose escalation study. The primary objective of the study is to establish the MTD of YQ23 as a single agent and the MTD when given in combination with pembrolizumab, by evaluating the incidence of dose-limiting toxicities (DLT).
In Stage 1, trial subjects will be enrolled successively in the treatment cohorts of 5 dose levels of YQ23. Each subject will receive an intravenous fixed dose of YQ23 weekly in one of the treatment cohorts. Stage 2 will start only when the MTD of single agent YQ23 has been established in Stage 1. In Stage 2, trial subjects will be enrolled successively in combo therapy dose cohorts starting with the lowest tested dose of YQ23 up to the MTD established in Stage 1. In each cohort of Stage 2, a fixed dose of 200 mg pembrolizumab will be given every 3 weeks on the same day following YQ23 administration.
Dose escalation decision will be made by an Independent Data Safety Monitoring Committee (DSMC) as determined by the DLT which is based on the incidence and intensity of drug-related adverse events (toxicities) occurring up to 8 days after the administration of the fourth dose of YQ23 in the single and combo therapy. The toxicities will be graded by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.
At least 3 evaluable subjects will be treated per dose cohort. Evaluable subjects are defined as subjects who have completed the first 4 doses of YQ23 and the safety assessment at Day 8 post YQ23 Dose 4, or subjects who have discontinued treatment due to a DLT. Dose escalation will only be started after all subjects in the previous cohort have completed assessments at Day 8 post Dose 4 of YQ23 in the single and combo therapy dose escalations. A satisfactory review of the safety and tolerability data by the DSMC is required before any dose escalation.
Following a 3+3 design, the MTD is defined as the highest dose level at which six patients are treated and one DLT has been observed, or three patients are treated and no one has experienced a DLT. If no DLT is found, the highest dose will be determined as the MTD.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||3+3 dose escalation study composed of 2 stages. Single agent in Stage 1 (as defined as arm 1) and combination therapy in Stage 2 (as defined in arm 2)|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib, Open-label, Dose-escalation Study of YQ23 as a Single Agent and in Combination With Pembrolizumab Administered to Patients With Advanced Solid Tumors|
|Actual Study Start Date :||August 21, 2020|
|Estimated Primary Completion Date :||October 31, 2021|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Stage 1: Single agent
Intravenous weekly dose of YQ23 for 4 weeks with an ascending dose levels of 20, 30, 60, 90 and 120 mg/kg will be evaluated.
YQ23 as a single agent will be given in Stage 1.
Experimental: Stage 2: Combination Therapy
Intravenous weekly dose of YQ23 for 4 weeks with an ascending dose levels from 20 mg/kg to the MTD obtained from Stage 1 in combination of a fixed dose of 200 mg intravenous pembrolizumab given on the same day following YQ23 administration and every 3 weeks thereafter.
Combination Product: Pembrolizumab
Pembrolizumab will be given in combination with YQ23 in Stage 2
- Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) of YQ23 as single agent (Stage 1) and when in combination with Pembrolizumab (Stage 2) [ Time Frame: From start of study until 12 weeks after last dose ]
The incidence and severity of AEs and SAEs including the following cardiac events of interests evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v5.0:
- Cardiac troponin I increase
- Ejection fraction decrease
- Electrocardiogram corrected QT interval prolongation
- Creatine phosphokinase increase
- Establishment of MTD for YQ23 as single agent (Stage 1) and when in combination with Pembrolizumab (Stage 2) [ Time Frame: From the start of treatment until Day 8 post Dose 4 of YQ23 at each dose level (in both stages) ]MTD will be evaluated by the incidence of DLT for which it will be determined based on the incidence and intensity of drug-related adverse events (toxicities) occurring up to 8 days after the administration of the fourth dose of YQ23 in the single and combo therapy dose escalations. The toxicities will be graded by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) v5.0.
- Pharmacokinetics of YQ23 as measured by plasma concentration in single agent group and combo therapy group [ Time Frame: Pre-dose, 0hour (End of infusion, EoI), 0.25hour, 0.5hour, 1hour, 2hours, 6hours, 12hours, 24hours, 48hours post-EoI of the initial dose and 0.5hour post-EoI Dose 4 ]Plasma level of YQ23 will be serially evaluated following dosing of study drug(s), and the maximum observed plasma concentration (Cmax) of YQ23 will be determined.
- Pharmacokinetics of YQ23 as measured by area under the plasma concentration-time curve in single agent group and combo therapy group [ Time Frame: Pre-dose, 0hour (End of infusion, EoI), 0.25hour, 0.5hour, 1hour, 2hours, 6hours, 12hours, 24hours, 48hours post-EoI of the initial dose and 0.5hour post-EoI Dose 4 ]Plasma level of YQ23 will be serially evaluated following dosing of study drug(s), and area under the plasma concentration-time curve of YQ23 will be determined.
- Pharmacokinetics of YQ23 as measured by terminal half-life in single agent group and combo therapy group [ Time Frame: Pre-dose, 0hour (End of infusion, EoI), 0.25hour, 0.5hour, 1hour, 2hours, 6hours, 12hours, 24hours, 48hours post-EoI of the initial dose and 0.5hour post-EoI Dose 4 ]Plasma level of YQ23 will be serially evaluated following dosing of study drug(s), and terminal half-life of YQ23 will be determined.
- Disease control rate (DCR) by YQ23 when given alone and when in combination with pembrolizumab [ Time Frame: This will be measured at Day 8 post YQ23 Dose 4 ]DCR is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) or stable disease (SD) using RECIST 1.1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04513067
|Contact: Yolanda Yan||+852 2133 firstname.lastname@example.org|
|Contact: Eric Nam||+852 2133 email@example.com|
|The University of Hong Kong Phase I Clinical Trials Centre||Recruiting|
|Hong Kong, Hong Kong|
|Contact: Kitty Leung +852 2255 6920 firstname.lastname@example.org|
|Principal Investigator: Thomas Yau, Dr.|
|Study Director:||Billy Lau, PhD.||New Beta Innovation Limited|